Generic Name

Sertraline

Mechanism

• Selective serotonin reuptake inhibitor (SSRI): Blocks serotonin (5‑HT) re‑uptake transporter (SERT) in presynaptic neurons.
• Increases extracellular serotonin concentration in the synaptic cleft, enhancing serotonergic neurotransmission.
• Secondary inhibition of norepinephrine and dopamine re‑uptake at high concentrations, but clinically minimal.
• No effect on presynaptic 5‑HT synthesis or degradation.

Pharmacokinetics

• Bioavailability: ~44 % after oral dosing; food reduces absorption by ~30 %.
• Onset: Clinical effect appears 1–2 weeks; plasma concentrations reach steady state within ~3–4 weeks.
• Metabolism: Primarily hepatic *CYP2B6* and *CYP2D6* (minor *CYP3A4* contribution).
• Half‑life: Terminal 26–42 h (parent drug)→t½ ≈ 4–7 days (active metabolite, N‑hydroxysulfonamide).
• Volume of distribution: ~5 L /kg.
• Elimination: ~75 % renal; 23 % fecal.
• Drug interactions: ↑t½/narrow therapeutic index with *CYP2D6* inhibitors (e.g., fluoxetine); ↓t½ with *CYP2D6* inducers (e.g., carbamazepine).

Indications

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)
• Obsessive‑Compulsive Disorder (OCD)
• Panic Disorder (PD)
• Post‑Traumatic Stress Disorder (PTSD)
• Premenstrual Dysphoric Disorder (PMDD)
• Pre‑operative anxiety (off‑label, limited evidence)

Contraindications

• Contraindications
• Concomitant use of monoamine oxidase inhibitors (MAOIs) within 14 days.
• Known hypersensitivity to sertraline or other SSRIs.
• Warnings
• Serotonin syndrome (especially with other serotonergic drugs).
• Hyponatremia: risk elevated in elderly or patients on diuretics.
• Abnormal liver function: monitor ALT/AST; dose adjustment or discontinuation may be needed.
• Potential for increased suicidality: mandatory surveillance in patients aged 18–25 y.
• Drug interactions: beware of QT prolongation with other QT‑extending agents.

Dosing

• Adults
• *Initial*: 50 mg once daily (preferably morning).
• *Maintenance*: 75–200 mg/day; titrate by 50 mg increments every 1–2 weeks.
• *Maximum*: 200 mg/day.
• Elderly (≥ 65 y)
• Start 25–50 mg, titrate slowly (≤ 50 mg every 4 weeks).
• Pregnancy/Lactation
• Category C; use only if benefit > risk.
• Minimal crossing of placenta; data on lactation suggest minimal risk but infant monitoring recommended.
• Renal/Hepatic Impairment
• Mild–moderate hepatic dysfunction: no dose adjustment, monitor liver enzymes.
• Severe hepatic or renal impairment: reduce dose, monitor for accumulation.
• Special Populations
• Pediatrics (12–17 y): 25 mg daily, titrate to 50 mg; safe and well‑tolerated.
• Children (< 12 y): not FDA‑approved; limited evidence for use.

Adverse Effects

• Common
• Nausea, vomiting, diarrhea.
• Sexual dysfunction (decreased libido, delayed ejaculation, anorgasmia).
• Insomnia or somnolence.
• Dry mouth, headache, tremor.
• Serious
• Serotonin syndrome: hyperthermia, tremor, autonomic instability.
• Suicidal thoughts, risk rising in adolescent/young adult population.
• Hyponatremia (especially in elderly).
• Severe GI bleeding when combined with NSAIDs or anticoagulants.
• QT prolongation rare; monitor ECG in patients with existing arrhythmias.

Monitoring

• Baseline & periodic labs
• CBC, CMP (especially ALT/AST).
• Serum electrolytes (Na⁺, K⁺) in elderly/influenced patients.
• Clinical
• Monitor for signs of serotonin syndrome.
• Assess weight/ BMI changes.
• Screen for depression severity (HAM-D, PHQ‑9) at baseline, 2‑4 weeks, and every 3 months.
• Cardiac
• ECG if QT prolongation risk factors, or if pulse > 100 bpm.
• Drug interaction
• Review concomitant serotonergic agents (e.g., triptans, tramadol).

Clinical Pearls

1. Early Switching – If inadequate response after 4–6 weeks at 100 mg, consider switching to a different SSRI or adding a low dose of lamotrigine before escalating dose.

2. Food Considerations – While food slightly reduces bioavailability, it *mitigates* the risk of nausea; give with or after meals if GI upset occurs.

3. Elderly Dosing – Start at a lower maintenance dose (25–50 mg/24 h); titrate more slowly to avoid fall risk due to dizziness.

4. Sexual Dysfunction Management – Offer lifestyle adjustment (e.g., reduce alcohol), switch to fluvoxamine, or add a dopamine agonist if significant impairment persists.

5. Suicidality Screening – For patients 18–25 y, use the Suicidal Ideation Attributes Scale (SIAS) at each visit until 6 months post‑initiating therapy.

6. Drug‑Drug Interaction Watch – Combine with triptans only after at least 5 days of sertraline to allow steady‑state levels, minimizing serotonin syndrome.

7. Compliance Aid – Place the bottle at the same location each morning; use a pill organizer for high‑dose regimens to reduce missed doses.

8. Pregnancy Follow‑up – In trimester II–III, monitor maternal serum sodium; infant follow‑up at birth for transient respiratory distress or feeding issues.

> *References*:

> 1. WHO Drug Information, “Sertraline.” 2023.

> 2. APA Clinical Practice Guidelines, 2022.

> 3. Goodman & Gilman's Pharmacological Basis of Therapeutics, 13th ed., 2022.

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